In the 1999 general election Prendergast stood as a National list candidate, ranked 30th on the party's list. However, the National Party did not gain enough of the party vote for Prendergast to enter Parliament. She considered running again at the 2002 election, but in 2001 Mark Blumsky announced his intention not to run for the mayoralty again, and endorsed Prendergast's mayoralty candidacy.

Prendergast was elected mayor in 2001 and re-elected in 2004 and 2007. During her time as Mayor, Prendergast instigated the policy of making Wellington the "Creative Capital". She has endorsed changing the Flag of New Zealand.[3]

In 2015 Prendergast accepted the role of ambassador for Alzheimer's New Zealand, having had personal experience of the disease - both her late father Denis and her mother Beverley Ferrier suffered the disease.[8]